Low Cytotoxicity Research Articles

Near-infrared probes based on the phenanthridinium for dynamic monitoring of viscosity fluctuations during mitophagy

Abnormal changes in the mitochondrial microenvironment can cause a variety of diseases. Consequently, based on the twisted intramolecular charge transfer (TICT) theory, three hemicyanine fluorescent probes 1a-c were designed and developed by linking the phenanthridine group with different electron donor groups for the dynamic detection of mitochondrial viscosity in this paper. They have the advantages of near-infrared emission, excellent pH stability and viscosity sensitivity. Optical experiments showed that the maximum absorption and emission wavelengths of the probes in different solvents located at 411 − 529 nm and 623 − 684 nm with large Stokes shifts of 133 – 230 nm. In addition, when the viscosity increased from 0.89 cP to 856 cP, their fluorescence intensities in glycerol enhanced by 115-fold, 83-fold and 303-fold compared with water, respectively. The fluorescence intensities of probes showed excellent fit to the Forster Hoffmann equation, and exhibited nearly OFF-ON response to viscosity. Moreover, the probe 1a with good photostability and low cytotoxicity could target mitochondria. It was verified that 1a also could detect variation in mitochondrial viscosity during autophagy by modelling starvation and drug-induced (rapamycin and nystatin) in HeLa cells. Therefore, this study provides a useful probe for the analysis of mitophagy process in HeLa cells by the viscosity variation of mitochondria.

Synthesis of temperature-sensitive boron, nitrogen and sulphur doped carbon dots and their applications

Boron-Sulfur-Nitrogen doped carbon dots (B, N, S-CDs) were prepared by a simple hydrothermal method using 2-Mercaptopyrimidine (C4H4N2S) and citric acid (C6H8N7•H2O) as raw materials. The B, N, S-CDs showed exceptional fluorescence response to Fe2+, TC. The results of the B, N, S-CDs are very promising for the detection of real water samples. In addition, the B, N, S-CDs had a good temperature response (reversible and recoverable fluorescence in the temperature range of 25–65︒C). The low cytotoxicity and in vitro cellular imaging properties exhibited by this carbon dot also greatly enhance their utility.

Development and In vitro and In vivo efficacy investigation of multifunctional, targeted, theranostic liposomes for imaging and photodynamic therapy of glioblastoma

The challenge of effectively diagnosing and treating glioblastoma, which has a high incidence and low survival rate, remains unresolved. Consequently, research efforts have increased to develop specific and effective diagnostic and therapeutic agents. In this study, N-acetyl glucosamine-modified, IR780-encapsulated, PEG-coated, nanosized, 68Ga-labeled, neutral, and positively charged theranostic liposomes were developed for GLUT1 targeting for PET/CT and NIR imaging and PDT/PTT of GBM. Characterization, in vitro release profile, stability, radiolabeling efficiency, and labeling stability were evaluated. In vitro cell uptake studies were conducted in RG2 and U87 GBM cell lines, NIR images were obtained in the RG2 and U87 cell lines, and fluorescence microscope images were obtained in the RG2 cell line. PDT/PTT activities were assessed after exposure to NIR light (808 nm, 0.8–1 W/cm2). Cytotoxicity was studied in RG2, U87, and L929 cell lines. In vivo studies were performed in GBM model nude mice. The liposomes had an optimum mean particle size (181–193 nm), high encapsulation efficiency (79–84 %), and zeta potential (−5 to −7 mV). The maximum 68Ga labeling efficiency was achieved with an incubation at 80 °C, pH: 3.5, and 5 min. Liposomes remained stable for 30 days at 4 °C. While the intracellular uptake of targeted formulations was higher than non-targeted ones, it was similar for positively charged and neutral formulations. In U87 and RG2 cell lines, cell viability remained above 50 % for liposomal formulations at a concentration of 1.5 μg/mL exposed to NIR light (808 nm, 0.8–1 W/cm2). The formulations showed significant PDT/PTT activity under NIR light and lower cytotoxicity in the L929 than in RG2 and U87 cell lines. In vivo bioluminescence images and biodistribution studies in U87 tumor-bearing nude mice revealed higher tumor uptake of targeted, IR780-encapsulated liposomal formulations in tumor tissue compared to non-targeted ones. Liposomal formulations showed higher tumor uptake than the free IR780 solution. The data suggest that targeted liposomes have potential as theranostic agents for PDT/PTT and multifunctional glioblastoma imaging.

Corked Microcapsules Enabling Controlled Ultrasound-Mediated Protein Delivery.

While ultrasound represents a facile, portable, and noninvasive trigger for drug delivery vehicles, most reported ultrasound-triggered drug delivery vehicles predominately present "burst" release profiles that are hard to control after the initial activation stimulus. Herein, we report a submerged electrospraying technique to fabricate protein-loaded microcapsules in which silica "corks" are embedded within the microcapsule shell. Upon the application of an ultrasound trigger, the corks can be perturbed within the shell, allowing for the release of the protein payload through a phantom tissue mimic to a degree proportional to the number/time of pulses applied. Specifically, multiple ultrasound pulses were shown to enable a 15- to 23-fold increase in the rate of release of the model bovine serum albumin protein payload relative to no ultrasound being applied, with release returning to a lower level when the ultrasound stimulus was removed. Coupled with the low cytotoxicity of the vehicle components, the corked microcapsules show promise for expanding the potential to use ultrasound to facilitate both on-demand and pulsatile release profiles.

Dual-Activated Photoacoustic Probe for Reliably Detecting Hydroxyl Radical in Ischemic Cardiovascular Disease in Mouse and Human Samples.

Cardiovascular disease (CVD) is a chronic disease characterized by the accumulation of lipids and fibrous tissue within the arterial walls, potentially leading to vascular obstruction and an increased risk of heart disease and stroke. Hydroxyl radicals play a significant role in the formation and progression of CVD as they can instigate lipid peroxidation, resulting in cellular damage and inflammatory responses. However, precisely detecting hydroxyl radicals in CVD lesions presents significant challenges due to their high reactivity and short lifespan. Herein, we present the development and application of a novel activatable optical probe, Cy-OH-LP, designed to detect hydroxyl radicals in lipid-rich environments specifically. Built on the Cy7 molecular skeleton, Cy-OH-LP exhibits near-infrared absorption and fluorescence characteristics, and its specific response to hydroxyl radicals enables a turn-on signal in both photoacoustic and fluorescence spectra. The probe demonstrated excellent selectivity and stability in various tests. Furthermore, Cy-OH-LP was successfully applied in an in vivo model to detect hydroxyl radicals in mouse models, providing a potential tool for diagnosing and monitoring AS. The biosafety of Cy-OH-LP was also verified, showing low cytotoxicity and no significant organ damage in mice. The findings suggest that Cy-OH-LP is a promising tool for the specific detection of hydroxyl radicals in lipid-rich environments, providing new possibilities for research and clinical applications in the field of oxidative stress-related diseases.

Synthesis of Benzannulated Spiroketals Derived From Stigmasterol and Sitosterol by Pd‐Catalyzed Spirocyclization. NMR and X‐ray Characterization. Evaluation of Cytotoxicity and Anti‐Inflammatory Activity

ABSTRACTFive new benzannulated steroid spiroketals were synthesized by Pd‐catalyzed spiroketalization of 5α and 5β‐alkynediols derived from stigmasterol and sitosterol. The detailed nuclear magnetic resonance (NMR) and X‐ray characterization of the newly obtained spiroketals are presented. While the obtained compounds showed null or very low cytotoxicity, two of them inhibited more than 60% of the nitrous oxide production in J774A.1 macrophages stimulated with LPS, showing promising properties as anti‐inflammatory agents.

Novel Alkynylamide-Based Nonpeptidic Allosteric Inhibitors for SARS-CoV-2 3-Chymotrypsin-like Protease.

Although the coronavirus disease 2019 (COVID-19) crisis has passed, there remains a necessity for continuous efforts toward developing more targeted drugs and preparing for potential future virus attacks. Currently, most of the drugs received authorization for the treatment of COVID-19 have exhibited several limitations, such as poor metabolic stability, formidable preparation, and uncertain effectiveness. It is still significant to develop novel, structurally diverse small-molecule antiviral drugs targeting SARS-CoV-2 3-chymotrypsin-like protease (3CLpro). Herein, we report a class of alkynylamide-based nonpeptidic 3CLpro inhibitors that can be prepared conveniently by our previously developed one-pot synthetic method. The structure-activity relationships of alkynylamides as SARS-CoV-2 3CLpro inhibitors have been carefully investigated and discussed in this study. The two stereoisomers of the resulting molecules exhibit stereoselective interaction with 3CLpro, and the optimized compound (S,R)-4y inhibits 3CLpro with high potency (IC50 = 0.43 μM), low cytotoxicity, and acceptable cell permeability. Compound (S,R)-4y presents as a noncovalent inhibitor of 3CLpro against SARS-CoV-2 by the time-dependent inhibition assay (TDI) and mass spectrometry analysis. The Lineweaver-Burk plots, binding energy, surface plasmon resonance, and molecular docking studies suggest that (S,R)-4y specifically binds to an allosteric pocket of the SARS-CoV-2 3CLpro. These findings provide a novel class of nonpeptidic alkynylamide-based allosteric inhibitors with high selectivity against SARS-CoV-2 3CLpro featured by a simplified one-pot synthesis at room temperature in air.

Identification of adenosine analogues as nsp14 N7‑methyltransferase inhibitors for treating coronaviruses infection

Coronaviruses are RNA viruses that have coevolved with humans and animals over time, exhibiting high mutation rates and mortality rates upon epidemic outbreaks. The nonstructural protein (nsp14) is crucial for various coronaviruses processes, including genome replication, protein translation, virus particle assembly, and evasion of host immunity via RNA methylation modification. In this study, a series of adenosine analogs were designed, synthesized, and evaluated for their inhibitory activities. Among them, MTI013 exhibited the strongest nsp14 MTase inhibition and antiviral activity, with an IC50 of 10.33 μM in HCoV-229E-infected Huh7 cells, along with low cytotoxicity. When combined with the RdRp inhibitor ATV014, MTI013 showed a synergistic antiviral effect, indicating its potential both as a standalone therapy and in combination treatments. Furthermore, MTI013 displayed high selectivity against the SARS-CoV-2 nsp10-nsp16 complex and five human methyltransferases. These results offer valuable structural insights for future exploration of nsp14 as a drug target for SARS-CoV-2 and other coronaviruses.

Combinatorial Synthesis of Alkyl Chain-Capped Poly(β-Amino Ester)s for Effective siRNA Delivery.

Poly (β-amino ester) (PBAE) is a class of biodegradable polymers containing ester bonds in their main chain, extensively investigated as cationic polymer carriers for siRNA. Most current PBAE carriers rely on termination with hydrophilic or charged amines. In this study, a polymer platform consisting of 168 PBAE polymers with hydrophobic alkyl chain terminals is constructed through sequential aza-Michael addition. A large number of effective carriers are identified through in vitro screening of the PBAE platform for siLuc delivery to HeLa-Luc cells. Specifically, PA8-C6 and PA8-C8 achieve remarkable gene knockdown efficacies of up to 80% with low cytotoxicity. Certain materials from the PA2 and PA5 series demonstrate potent siRNA delivery capabilities associated with elevated cytotoxicity. The pKa value of PBAE is predominantly determined by the hydrophilic amine side chains rather than the end-capping groups. A pKa range of ≈6.2-6.5 may contribute to the excellent delivery capability for PA8 series carriers. The co-formulation of PBAE carriers with helper lipids leads to the reduced size and surface charges of the polyplex NPs with siRNA, consequently decreasing the cytotoxicity and enhancing siRNA delivery efficacy. These findings hold significant implications for the development of novel degradable polymer carriers for siRNA delivery.

Water-soluble sulfur quantum dots as a potential sensitive fluorescent probe for quercetin detection and cell imaging

A simple fluorescent quenching probe based on polyethylene glycol-400 capped sulfur quantum dots (PEG-SQDs) was fabricated to determine quercetin (QT) quantitatively. As anticipated, the PEG-SQDs exhibited favourable luminescent properties, stability and low cytotoxicity. QT effectively quenched the fluorescence of the PEG-SQDs through static quenching and the inner filter effect. Moreover, the PEG-SQDs showed rapid QT detection within a linear range of 0.100–45.0 μM, with a limit of detection of 0.014 μM (3σ/k). This fluorescent probe successfully detected QT in human serum, quercetin supplement capsules and red wine, achieving a standard recovery of 92.6 %–105 %.

Superior Tumor Cell Uptake by Mono- and Tri-Nuclear Rhodamine-Gadolinium(III) Agents.

The synthesis and characterization of a novel trinuclear rhodamine-Gd(III) complex, along with two analogous mononuclear rhodamine-Gd(III) complexes, are reported. All complexes displayed good selectivity in a human glioma cell line (T98G) when compared to a glial cell line (SVG p12), with low cytotoxicities. Superior tumor cell uptake for these Gd(III) complexes was observed at lower incubation concentrations compared to previously-reported delocalized lipophilic cations such as a rhodamine-lanthanoid(III) probe and Gd(III)-arylphosphonium complexes, with ca. 150 % and 250 % increases in Gd uptake, respectively.

Polymeric artificial heart valves derived from modified diol-based polycarbonate polyurethanes

A series of polycarbonate silicone polyurethanes (SiPCUs) have been synthesized to develop elastomers with the mechanical properties, biostability, and biocompatibility required for artificial heart valve manufacturing. In these SiPCUs, the polar functional group 4,4′-dicyclohexylmethane diisocyanate (HMDI) was incorporated into the soft segment 1,6-poly (hexamethylene carbonate) diol (PCDL) to form the modified macromolecular diol, PCDL-HMDI-PCDL. The hard segment consisted of HMDI and the chain extenders 1,4-butanediol and 1,3-bis(4-hydroxybutyl)-1,1,3,3-tetramethyl disiloxane (BHTD). The synthesized PHC-PCUB improves the excessive microphase separation caused by the introduction of PDMS. This material possesses good physicochemical properties, long-term oxidative degradation stability, and comparatively low mechanical performance loss after degradation. Compared to the commercially available bioprosthetic heart valve (BHV) material Glut-PP, PHC-PCUB demonstrated enhanced biocompatibility, good thromboresistant properties, less calcification, and higher endothelial cell adhesion. Furthermore, valve prototypes fabricated with PHC-PCUB showed improved hemodynamic performance under various simulated conditions, highlighting the potential of PHC-PCUB as an advanced material for valve leaflets. Statement of SignificanceArtificial heart valves are crucial for treating valve diseases, and polyurethane-based valves present a promising alternative due to their durability, strong biocompatibility, and customizable properties. This study improves the biostability and post-degradation mechanical properties of siloxane polyurethanes by reducing the content of polydimethylsiloxane (PDMS) and adding modified diol (PCDL-HMDI-PCDL). By integrating hexamethylene diisocyanate (HMDI) and chain extenders, we developed polycarbonate siloxane polyurethanes (SiPCUs) that improve phase mixing, mechanical strength, and oxidative stability. These SiPCUs also exhibit good thromboresistance and calcification resistance, low cytotoxicity, and promote cell adhesion, positioning them as highly promising materials for heart valve leaflets, effectively addressing the limitations of current mechanical and bioprosthetic valves.

Water-soluble neutral octahedral chalcogenide tungsten and molybdenum {M6Q8} clusters with P(C2H4CONH2)3 ligand

Developing the chemistry of octahedral chalcogenide molybdenum and tungsten cluster complexes in the context of applications in biology and medicine, in this work a series of water-soluble neutral cluster complexes [{M6Q8}(P(C2H4CONH2)3)6] (M = Mo, W; Q = S, Se) have been obtained by simultaneous replacement of inner and terminal halide ligands in [{M6I8}I6]2− with chalcogenide and organic phosphine ligands and characterized by single-crystal X-ray diffraction analysis, 1H and 31P NMR spectroscopies, elemental analysis, and UV–vis spectroscopy. The amide groups of the organic ligands, on the one hand, contribute to the solubility of the resulting clusters in water and, on the other hand, are able to form an extensive network of hydrogen bonds, leading to the crystallization of the complexes from aqueous solutions. Despite this fact, the complexes have sufficient solubility and stability in aqueous solutions, which made it possible to demonstrate their low cytotoxicity on Hep-2 cells (IC50 were not reached even at concentration up to 4 mM). The resulting clusters are among the most biocompatible of the octahedral clusters studied to date and are the starting point for the development of a new family of X-ray contrast agents.

Magnetic lipid-poly(lactic-co-glycolic acid) nanoparticles conjugated with epidermal growth factor receptor antibody for dual-targeted delivery of CPT-11

To entrap sparingly water-soluble drugs like CPT-11 (irinotecan), the poly(lactic-co-glycolic acid) (PLGA) nanoparticle (NP) is highly favored due to its low cytotoxicity and approval for clinical use. On the other hand, entrapping hydrophobic oleic acid-coated iron oxide magnetic nanoparticles (OMNP) in PLGA NP can provide a nanovehicle for magnetically targeted drug delivery. Our goal in this study is to develop a new dual-targeted magnetic lipid-polymer NP for the delivery of CPT-11. We first co-entrap OMNP and CPT-11 in self-assembled lipid-PLGA NP to prepare OLNP@CPT-11. The OLNP@CPT-11 surface was modified with an epidermal growth factor receptor (EGFR) antibody Cetuximab (CET), which can actively target the overexpressed EGFR on the U87 glioblastoma cell surface. The OLNP-CET@CPT-11 enables dual targeting through both external magnetic guidance and CET-mediated active targeting. The NP was characterized for physicochemical properties using various analytical techniques. In vitro study confirms ligand-receptor interaction results in enhanced endocytosis of OLNP-CET@CPT-11 by U87 cells, which offers increased cytotoxicity and elevated cell apoptosis rates. Furthermore, magnetic guidance of OLNP-CET@CPT-11 to U87 cells can induce cell death exclusively in the magnetically targeted zone. The dual-targeted strategy also provides the best therapeutic efficacy against subcutaneously implanted U87 tumors in nude mice with intravenously delivered OLNP-CET@CPT-11.

A Fluorescent Probe Containing Triphenylamine-Benzofuranone Moiety for Detecting Cysteine and Imaging in Living Pulmonary Cells Under Hypercapnia.

In this work, a fluorescent probe TPB-Cys derived from triphenylamine-benzofuranone was developed for monitoring the cysteine (Cys) level and imaging in living pulmonary cells under hypercapnia condition. A systematic hypoxia module was tried to cover both the in-solution test and pulmonary cellular imaging. The hypoxia condition did not obviously affect the fluorescence response signal during the in-solution test. The fluorescence signal at 540 enhanced in a dose-dependent enhancement along with the increase of the Cys concentration. The probe showed the advantages including relatively long linear range, high sensitivity, high stability, and high selectivity. With low cyto-toxicity, TPB-Cys achieved the monitoring of the endogenous Cys level in living pulmonary cells. Furthermore, it also realized the visualization of the affection of the hypoxia and hypoxia recovered conditions. This work was informative for both the accurate diagnosis and potential medical techniques.

Preparation, characterization, stability and application of the H-type aggregates lutein/whey protein/chitosan nanoparticles

Natural lutein is liposoluble and has powerful antioxidant activity, which can be self-aggregated to form H-type aggregates in organic-water systems. However，its application is limited by poor solubility and high instability. Here, whey proteins/chitosan-coated H-type aggregates lutein nanoparticles (NPs) were fabricated via a bottom-up layer-by-layer self-assembly technique. The optimal conditions for the preparation of the NPs (173.3 nm) were determined by the Dynamic Light Scattering and UV–vis spectroscopy. Briefly, three proteins, WPI and WPC and BSA were used to fabricate polysaccharide-protein nanocarriers to encapsulate the lutein. These spectroscopy studies indicated that chitosan and BSA formed hydrophobic microdomain by the intermolecular electrostatic attraction force with remarkable changes of secondary structure in protein. The morphology revealed that the NPs were nearly spherical. The EE of the NPs was >90 %, with a LC of up to 28.32 %. Lutein in NPs can be stabilized as H-type aggregates at different temperatures and pH-values. Additionally, the cytotoxicity test of the NPs on L929 and Caco-2 cells showed that NPs had low cytotoxicity in a limited concentration range. Results indicated that whey protein/chitosan-coated lutein nanoparticles significantly improved water dispersion and stability of lutein and its aggregates, thus broadening their application in nutrient delivery system.

A chemoselective and enantioselective fluorescent probe for D-Histidine in aqueous solution and living cells

D-Histidine (D-His) holds clinical relevance in the pathogenesis of various diseases, including neurological disorders and chronic kidney disease. The specific detection of D-His within biological systems holds profound significance for the early diagnosis of associated ailments. However, the design of probes targeting D-His is inherently challenging due to the presence of its enantiomers. Herein, we introduce a novel D-His fluorescence probe, designated as (S)-1, based on the 1,1’-bi-2-naphthol (BINOL) framework. Remarkably, (S)-1 demonstrates exceptional chemoselectivity and enantioselectivity towards D-His, achieving a remarkable detection limit of 4.896nM. Moreover, the low cytotoxicity and superior biocompatibility of (S)-1 facilitate fluorescence imaging of D-His within living cellular environments. NMR analysis and theoretical calculations have substantiated the reaction products and elucidated the recognition mechanism. To our knowledge, (S)-1 stands as the inaugural BINOL-based fluorescence probe for the specific detection of D-His among the 20 common amino acids. These findings provide pivotal groundwork for the development of chiral fluorescence probes targeting amino acids.

Unveiling the antimetastatic activity of monoterpene indole alkaloids targeting MMP9 in cancer cells, with a focus on pharmacokinetic and cellular insights

Distant metastasis, together with acquired resistance, limits the therapeutic impact of chemotherapy and molecularly targeted therapies. The properties of the tumor microenvironment determine how sensitive or resistant various cancers are to specific pharmacological treatments. Matrix metalloproteinase 9 (MMP9) is widely known for its ability to break down the extracellular matrix and it also modulates the motility of cancer cells. Here, our goal was to identify compounds that target MMP9 and evaluate their capacity to inhibit the motility of cancer cells. The anti-metastatic effect of monoterpene indole alkaloids (MIAs) on cell viability and motility was evaluated by MTT assay, migration assay, invasion assay, qRT-PCR, pathway-focusedexpression analysis, Western blotting, reporter assay, molecular docking simulation, and target prediction. MIA compounds target MMP9. MIAs inhibited the expression of p-EGFR, p-Akt, p-JNK and cyclin D1. Additionally, MIAs had predicted favorable pharmacokinetic profile and drug-like properties. Furthermore, among the MIA compounds lyaloside and 5(S)-5 carbomethoxy strictosidine had low cytotoxicity and regulated cancer-related signaling, including cell migration, cell invasion, epithelial–mesenchymal transition and immune evasion. Our findings demonstrated that the MIAs used in this study have potential anti-metastasis properties that occur via MMP9-mediated regulation of cancer signaling and have the potential to be used therapeutically at safe doses.

Go with the flow: An in vitro model of a mature endothelium for the study of the bioresponse of IV injectable nanomedicines

The first exposure of intravenously (IV) administered nanomedicines in vivo is to endothelial cells (ECs) lining blood vessels. While it is known that in vitro endothelium models to assess responses to circulating nanoparticles require shear stress, there is no consensus on when and how to include it in the experimental design. Our experimental workflow integrates shear stress by featuring a flow-induced mature endothelium (14 days) and a flow-mediated nanoparticle treatment. The mature endothelium model exhibited distinct features that indicated a structurally stable and quiescent monolayer. Upon treatment with iron sucrose under dynamic conditions, there was a lower nanoparticle uptake, lower cytotoxicity, and decreased expression of activation markers compared to the static control. This response was attributed to glycocalyx expression, predominantly observed on the mature endothelium. In conclusion, our proposed in vitro endothelium model can be leveraged to understand the dynamics of IV injectable nanomedicines at the initial nano-bio interface in veins immediately post-injection.

Synthesis of novel skipped diene-3-halocoumarin conjugates as potent anticancer and antibacterial biocompatible agents

Cancer and bacterial infections are persistent nightmares for human health, which are now aggravated by the development of new types of cancer and pathogenic bacteria, as well as their resistance to prescribed drugs. To be part of a hopeful awakening, this work aimed to synthesize four novel skipped diene-3-halocoumarin conjugates coded SDC1-SDC4 and explore their biosafe functions as anticancer and antibacterial alternatives. In the first step of their synthesis, mequinol reacts with ethyl-2-haloacetoacetate through a H2SO4-catalyzed Pechmann reaction, yielding 3-halo-6-methoxy-4-methylcoumarins. The in situ-generated Vilsmeier-Haack reagent formylated these trifunctionalized coumarins to create their 7-carbaldehyde congeners. Finally, the target conjugates were prepared by condensing the latter compounds with 2,4-pentadione through the modified Claisen-Schmidt reaction. The molecular structures involving their stereochemistry were established for SDC1-SDC4 by analyzing their spectra released from FTIR, 1H NMR, 13C NMR, and HRMS. On the other hand, the anticancer and cytotoxicity of these conjugates were investigated against eight cancer and three healthy cell lines, respectively, using an MTT-probing technique. Four pathogenic and three commensal aerobes were the microbes utilized to evaluate the antibacterial and microbiota compatibility, respectively, employing a broth microdilution methodology. The results indicated that the conjugate with the highest anticancer attribute and lowest cytotoxicity was SDC1, while SDC2 demonstrated the greatest antibacterial attribute with minimal microbiota toxicity. These findings projected the influence of a 3-position substitute of the coumarin backbone on the biological activities under research. From these, it is concluded that the chemical structures of SDC1 and SDC2 may represent potent anticancer cytocompatible and antibacterial microbiota-compatible scaffolds, respectively.